1,720,971 research outputs found
Nephroprotective effect of the HMG-CoA-reductase inhibitor cerivastatin in a mouse model of progressive renal fibrosis in Alport syndrome
No full textBackground. Alport syndrome is caused by mutations in genes encoding for the alpha 3, alpha 4 or alpha 5 chain of type IV collagen leading to excessive production of fibrotic tissue and end-stage renal failure. HMG-CoA-reductase-inhibitors exhibit pleiotropic effects by which they modulate the production of connective tissue. The aim of this study was to examine the anti-fibrotic effect of the HMG-CoA-reductase-inhibitor, cerivastatin, in COL4A3 knockout mice, an animal model of Alport syndrome with progressive renal fibrosis. Methods. Forty homozygous COL4A3 knockout mice received cerivastatin, starting 28 or 49 days after birth. Mice were sacrificed at day 52 or 66 after birth. Immunohistochemistry against laminin and fibronectin was performed. Inflammatory cell infiltration was determined by F4/80- and CD3-staining. Myofibroblasts were identified by an alpha-smooth muscle actin staining. Expression of the profibrotic cytokines, TGF-beta 1 and CTGF, were determined by immunoblot. Results. The lifespan of treated COL4A3 knockout mice was increased by 28% compared with untreated animals (71 +/- 6 vs 91 +/- 9 days, P < 0.01). Early cerivastatin treatment reduced cholesterol levels (113 +/- 13 vs 141 +/- 19 mmol/l in untreated animals, P < 0.05) and serum urea (164 vs 235 mmol/l, day 66, P < 0.05). Treatment also decreased proteinuria (5.5 vs 12 g/l at day 66, P < 0.05). Deposition of laminin and fibronectin, expression of TGF-beta and CTGF was reduced. Infiltration of T-cells and macrophages as well as myofibroblasts appeared to be reduced in kidneys from cerivastatin-treated mice. Conclusion. Cerivastatin prolongs the lifespan of COL4A3 knockout mice, reduces proteinuria and delays uraemia. These effects are associated with decreased renal fibrosis and a reduction of inflammatory cell infiltration
Antifibrotic, nephroprotective potential of ACE inhibitor vs AT1 antagonist in a murine model of renal fibrosis
No full textBACKGROUND: Several studies have shown antifibrotic effects of angiotensin converting enzyme (ACE) inhibitors as well as of angiotensin receptor 1 (AT1) antagonists, however, prospective trials with clinical end points comparing these effects do not exist. COL4A3-/- mice develop a non-hypertensive progressive renal fibrosis. We used this animal model to compare the potential of ACE inhibitor vs AT1 antagonist to prevent renal fibrosis irrespective of blood pressure-dependent involvement by the renin system. METHODS: COL4A3-/- mice were treated with placebo, ramipril or candesartan. Blood pressure, proteinuria, serum urea and lifespan were monitored. Renal matrix was characterized by immuno-histochemistry, light and electron microscopy. Further biochemical analysis was provided using cDNA microarray and western blot techniques. RESULTS: Untreated mice died of renal failure after 71+/-6 days. Ramipril and candesartan both delayed onset and reduced the extent of proteinuria. Both had minor effects on blood pressure and postponed onset of uraemia. Ramipril increased lifespan by 111% to 150+/-21 days (P<0.01), whereas candesartan resulted in only a 38% prolongation to 98+/-16 days (P<0.01). Ramipril reduced glomerular and tubulo-interstitial fibrosis and numbers of activated fibroblasts to a greater extent than candesartan. Microarray and western blot analysis revealed a higher antifibrotic potential of ramipril in terms of downregulation of TGFbeta, connective tissue growth factor, metalloproteinases and extracellular matrix proteins. CONCLUSIONS: The results indicate an antifibrotic, nephroprotective effect of ACE inhibitors and AT1 antagonists in an animal model of progressive renal fibrosis. The greater antifibrotic effect of ramipril at the maximal therapeutic doses employed may not be explained by different antiproteinuric or blood pressure lowering properties, but by-in contrast to candesartan-its ability to hinder the proinflammatory, profibrotic activation of the angiotensin receptor 2
A Cutting-Edge Magnetic Immunocapture Method to Isolate Cell-Type-Specific Mitochondria from Complex Neural Tissue
Get PDFBest Undergraduate Poster (Discovery Category) - OSU CBI Research Day 2025Alterations in neuronal and glial metabolism contribute to numerous neurodegenerative diseases, and the crosstalk between these two cell types (i.e., axoglial metabolic coupling) is at the center of extensive investigation. Metabolic alterations frequently culminate in mitochondrial dysfunction, but so far it has proven challenging to obtain cell-type-specific metabolic data from neuronal or glial mitochondria in mouse models of injury or disease. Magnetic immunocapture of genetically tagged mitochondria has emerged as a powerful strategy, yet existing methods are either incompatible with sensitive downstream multi omic workflows or not yet tested in complex tissues with highly heterogeneous cell populations. Here, I refined the “MITO-Tag” approach, which leverages a Cre dependent 3×HA EGFP OMP25 epitope tag localized to the outer mitochondrial membrane. Following enzymatic and mechanical dissociation, mitochondria were rapidly immunopurified from cortical neurons, oligodendrocyte lineage cells, and—accomplished here for the first time—peripheral nerve axons using anti-HA magnetic beads in liquid chromatography-tandem mass spectrometry (LC-MS/MS)-compatible KPBS buffer. This method yields specific and structurally intact mitochondria, as confirmed by live-organelle imaging and Western blotting for compartment-specific markers (COXIV, VDAC, citrate synthase), with minimal contamination from other organelles. Proteomic analysis of brain-derived immunoprecipitates (IPs) revealed mitochondrial enrichment comparable to existing magnetic immunopurification workflows. By enabling multi-omic mitochondrial profiling from moderate-abundance cell types within complex tissues, this method provides a versatile tool for investigating mitochondrial involvement in neurological disease and injury in vivo. Notably, isolation from peripheral nerve axons now offers the ability to characterize Wallerian degeneration and axoglial metabolic coupling mechanisms at an unprecedented resolution.NIH R01NS123450-01NIH R01NS111024-02OSU College of Engineering Thesis Research Grant2025 CAN-ACN Travel GrantNo embargoAcademic Major: Biomedical Engineerin
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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